The Challenge of Developing a Herpes Simplex Virus 2 Vaccine

Overview

Journal Expert Rev Vaccines

Date 2012 Dec 21

PMID 23252387

Citations 35

Authors

Lesia K Dropulic

Jeffrey I Cohen

Affiliations

Soon will be listed here.

Abstract

HSV infections are prevalent worldwide. A vaccine to prevent genital herpes would have a significant impact on this disease. Several vaccines have shown promise in animal models; however, so far these have not been successful in human clinical studies. Prophylactic HSV vaccines to prevent HSV infection or disease have focused primarily on eliciting antibody responses. Potent antibody responses are needed to result in sufficiently high levels of virus-specific antibody in the genital tract. Therapeutic vaccines that reduce recurrences need to induce potent T-cell responses at the site of infection. With the increasing incidence of HSV-1 genital herpes, an effective herpes vaccine should protect against both HSV-1 and HSV-2. Novel HSV vaccines, such as replication-defective or attenuated viruses, have elicited humoral and cellular immune responses in preclinical studies. These vaccines and others hold promise in future clinical studies.

Citing Articles

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Immunological Considerations for the Development of an Effective Herpes Vaccine.

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A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.

Wang K, Jordan T, Dowdell K, Herbert R, Moore I, Koelle D PLoS Pathog. 2024; 20(9):e1012477.

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Owen E, Jama M, Nahal B, Clarke E, Obasi A BMJ Glob Health. 2024; 9(7).

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References

Koelle D, Chen H, GAVIN M, Wald A, Kwok W, Corey L . CD8 CTL from genital herpes simplex lesions: recognition of viral tegument and immediate early proteins and lysis of infected cutaneous cells. J Immunol. 2001; 166(6):4049-58. DOI: 10.4049/jimmunol.166.6.4049. View

Vagvala S, Thebeau L, Wilson S, Morrison L . Virus-encoded b7-2 costimulation molecules enhance the protective capacity of a replication-defective herpes simplex virus type 2 vaccine in immunocompetent mice. J Virol. 2008; 83(2):953-60. PMC: 2612392. DOI: 10.1128/JVI.02022-08. View

Ahn K, Meyer T, Uebel S, SEMPE P, Djaballah H, Yang Y . Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47. EMBO J. 1996; 15(13):3247-55. PMC: 451885. View

Mark K, Wald A, Magaret A, Selke S, Olin L, Huang M . Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis. 2008; 198(8):1141-9. PMC: 2667115. DOI: 10.1086/591913. View

Koelle D, Posavad C, Barnum G, Johnson M, Frank J, Corey L . Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of HSV-specific cytotoxic T lymphocytes. J Clin Invest. 1998; 101(7):1500-8. PMC: 508728. DOI: 10.1172/JCI1758. View

Hoshino Y, Dalai S, Wang K, Pesnicak L, Lau T, Knipe D . Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs. J Virol. 2004; 79(1):410-8. PMC: 538700. DOI: 10.1128/JVI.79.1.410-418.2005. View

Hoshino Y, Pesnicak L, Dowdell K, Burbelo P, Knipe D, Straus S . Protection from herpes simplex virus (HSV)-2 infection with replication-defective HSV-2 or glycoprotein D2 vaccines in HSV-1-seropositive and HSV-1-seronegative guinea pigs. J Infect Dis. 2009; 200(7):1088-95. PMC: 3826825. DOI: 10.1086/605645. View

Mertz G, Ashley R, Burke R, Benedetti J, Critchlow C, Jones C . Double-blind, placebo-controlled trial of a herpes simplex virus type 2 glycoprotein vaccine in persons at high risk for genital herpes infection. J Infect Dis. 1990; 161(4):653-60. DOI: 10.1093/infdis/161.4.653. View

Looker K, Garnett G, Schmid G . An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Bull World Health Organ. 2008; 86(10):805-12, A. PMC: 2649511. DOI: 10.2471/blt.07.046128. View

10.

Basse G, Mengelle C, Kamar N, Ribes D, Selves J, Cointault O . Disseminated herpes simplex type-2 (HSV-2) infection after solid-organ transplantation. Infection. 2008; 36(1):62-4. DOI: 10.1007/s15010-007-6366-7. View

11.

Da Costa X, Jones C, Knipe D . Immunization against genital herpes with a vaccine virus that has defects in productive and latent infection. Proc Natl Acad Sci U S A. 1999; 96(12):6994-8. PMC: 22033. DOI: 10.1073/pnas.96.12.6994. View

12.

Straus S, Corey L, Burke R, Savarese B, Barnum G, Krause P . Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet. 1994; 343(8911):1460-3. DOI: 10.1016/s0140-6736(94)92581-x. View

13.

Yim K, Carroll C, Tuyama A, Cheshenko N, Carlucci M, Porter D . The cotton rat provides a novel model to study genital herpes infection and to evaluate preventive strategies. J Virol. 2005; 79(23):14632-9. PMC: 1287570. DOI: 10.1128/JVI.79.23.14632-14639.2005. View

14.

Meier J, Straus S . Comparative biology of latent varicella-zoster virus and herpes simplex virus infections. J Infect Dis. 1992; 166 Suppl 1:S13-23. DOI: 10.1093/infdis/166.supplement_1.s13. View

15.

de Bruyn G, Vargas-Cortez M, Warren T, Tyring S, Fife K, Lalezari J . A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects. Vaccine. 2005; 24(7):914-20. DOI: 10.1016/j.vaccine.2005.08.088. View

16.

Fleming D, McQuillan G, Johnson R, Nahmias A, Aral S, Lee F . Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. 1997; 337(16):1105-11. DOI: 10.1056/NEJM199710163371601. View

17.

Awasthi S, Lubinski J, Eisenberg R, Cohen G, Friedman H . An HSV-1 gD mutant virus as an entry-impaired live virus vaccine. Vaccine. 2008; 26(9):1195-203. PMC: 2680698. DOI: 10.1016/j.vaccine.2007.12.032. View

18.

Sakaoka H, Aomori T, Gouro T, Kumamoto Y . Demonstration of either endogenous recurrence or exogenous reinfection by restriction endonuclease cleavage analysis of herpes simplex virus from patients with recrudescent genital herpes. J Med Virol. 1995; 46(4):387-96. DOI: 10.1002/jmv.1890460416. View

19.

Stanberry L, Kern E, Richards J, Abbott T, Overall Jr J . Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease. J Infect Dis. 1982; 146(3):397-404. DOI: 10.1093/infdis/146.3.397. View

20.

Koelle D, Liu Z, McClurkan C, Cevallos R, Vieira J, Hosken N . Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor. Proc Natl Acad Sci U S A. 2003; 100(22):12899-904. PMC: 240716. DOI: 10.1073/pnas.2131705100. View